Previously, means such as oral administration, anal administration and injection have been adopted in the administration of physiologically active substances to the human body. For the oral administration, the substances are used in the form of capsules, tablets, granules etc. The substances orally administered, however, tend to be decomposed or deactivated by the action of a strong acid or an enzyme in the stomach before reaching the small intestine.
The stomach is an organ in which food ingested is digested. Carbohydrates in the food are decomposed to glucose through dextrin, oligosaccharide and maltose. Proteins are decomposed to amino acids through polypeptides, and fats are decomposed to glycerin and fatty acids. Although all these decomposition reactions may not always take place in the stomach, the physical, chemical and enzymic decomposition action in the stomach is considerably vigorous. It converts the food to a semiliquid rice gruel-like digest. As a result, the digestion in the duodenum and the digestion and absorption in the small intestine easily proceed. In particular, the physical decomposition action by the peristalsis of the stomach and the chemical decomposition action by the strong acidity of hydrochloric acid are non-selective, and considerably vigorous.
This nonselective, physical and chemical decomposition action is a negative factor with respect to most of the physiologically active substances administered orally. That is to say, many medicines and physiologically active substances are decomposed and deactivated in the stomach, and the efficacy thereof is reduced abruptly.
Furthermore, the digest is absorbed by the small intestine. The physiologically active substances administered orally are also digested in the stomach, carried to the entrance of the small intestine, and absorbed rapidly thereby, resulting in a rapid increase in the amount of the substances in the blood. It is however preferred that the speed of releasing the physiologically active substances from capsules is adjusted even in the small intestine, depending on their purpose. That is to say when it is desired, for medicines to act directly on the large intestine, such as chemotherapeutics against cancer of the large intestine, the speed should be adjusted so that they can reach the large intestine with almost no absorption of the medicines by the small intestine, when it is desired that physiologically active substances be swiftly absorbed by the small intestine, the speed should be adjusted so that they can be promptly released from capsules in the small intestine.
A technique of enclosing a physiologically active substance in a hard capsule formed of gelatin and coating an outer surface of the capsule with a specific protein resistant to digestion by gastric juice has also been proposed. Even according to this technique, however, the capsule is digested in the stomach.
The present inventors have disclosed a technique comprising making a capsule perforated with numerous holes which is formed of a viscous solution obtained by dissolving a natural polysaccharide/polyhydric alcohol composition in water, enclosing in the capsule a physiological active substance acting on the intestines, and coating the capsule with an edible hardened fat having a melting point of 35.degree. C. or above, in Japanese Unexamined Patent Publication No. 3-232815.
However, the capsule formed of the natural polysaccharide/polyhydric alcohol composition is poor in rigidity although it has flexibility, and has a tendency to physically break by the vigorous peristalsis of the stomach and intestines. In addition, the capsule perforated with numerous holes is very difficult to be produce on a commercial scale.
A protecting means has been demanded for allowing a physiologically active substance to act efficiently at any site from the small intestine to the large intestine, when it is orally administered. It must pass through the stomach without damage, prevent a loss in efficacy thereof in the stomach. That is to say, a capsule is desired which is scarcely dissolved in the stomach and can gradually release the physiologically active substance while passing from the small intestine to the large intestine.